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The discovery of methane (CH 4 ) accumulation in oxic marine and limnic waters has redefined the role of aquatic environments in the regional CH 4 cycle. Although CH 4 accumulation in oxic surface waters became apparent in recent years, the sources are still subject to controversial discussions. We present high-resolution in situ measurements of CH 4 concentration and its stable isotope composition in a stratified mesotrophic lake. We show that CH 4 accumulation in surface waters originates from a highly dynamic interplay between (oxic) CH 4 production and emission to the atmosphere. Laboratory incubations of different phytoplankton types and application of stable isotope techniques provide a first unambiguous evidence that major phytoplankton classes in Lake Stechlin per se produce CH 4 under oxic conditions. Combined field and lab results show that the photoautotroph community is an important driver for CH 4 production and its highly dynamic accumulation in oxic surface waters.

Purpose: The lack of drugs specifically assessed for paediatric use results in a widespread off-label drug use. The aim of this work is to identify experiences and attitudes towards paediatrics off-label prescribing in a university teaching paediatric hospital., Methods: A questionnaire of 24 items was sent by email to 409 paediatricians in February 2013., Data Collected: frequency of off-label prescribing, sources of information, concern about safety and adverse events with off-label drug use, proportion of parents informed and order with "off-label" mention., Results: Eighty questionnaires were returned. Over 81% of responders were familiar with the concept of off-label drugs prescribing. The most common reason given for off-label prescribing was for a younger age (74%) and for another indication (28%). They (79%) used a colleague's opinion and the most important sources of information used were the literature (72%), international guidelines (62%), the French National Formulary Vidal (56%) and national guidelines (46%). Although 54% of responders expressed concerns about safety about off-label prescription, only 29% had observed adverse event with off-label drug use. Two third of respondents informed the parents but off-label prescribing cannot be always explained to family. Many respondents (81%) did not write "off-label" mention on prescription. However, 52% stated that they would be willing to undertake off-label prescription monitoring with a local observatory., Conclusion: Our study describes the perceptions and attitudes of paediatrician's regarding off-label prescribing for children. Patient information and documentation in the patient file remain incomplete. The prospective collection of off-label prescription will locally be performed., (Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Off-label or unlicensed medicine use is very common in paediatric practice, ranging from 11 to 80 %, and is one of the predisposing factors for adverse events (23-60 %). Medicine indications are the third leading reason for doctors to perform off-label prescriptions., Objective: The aim of our study was to determine the prevalence and nature of off-label and unlicensed medicine prescriptions in children and propose methods for risk reduction and management., Setting: 475 bed maternity-paediatric university hospital., Method: Retrospective cross-sectional study lasting 1 day on new prescriptions issued over the previous 24 h by departments using electronic prescribing. Age and indication were compared to those in the French independent formulary Thériaque(®) database., Main Outcome Measure: Number of off-label/unlicensed prescriptions, number of patients, proportion of off-label/unlicensed prescriptions by age group, treatment class and International Non proprietary Name (INN), using the established classification., Results: A total of 315 prescription medicines were analysed for 120 patients, of average age 5.1 years old. For the classification of medicine utilisation, the majority of the medicines were prescribed as licensed (190/60.3 %), followed by off-label (115/36.5 %) and unlicensed (10/3.2 %) medicines. Alimentary tract, metabolic and nervous system medicines constituted the most widely prescribed ATC classes. At least 54 % of patients received an off-label/unlicensed medicine. The indications for these were mainly for off-label prescriptions (80/25.4 %) followed by medicines not evaluated for safety and regarding safety and efficacy in children (14/4.5 %). Pantoprazole was the most widely prescribed off-label INN for stress ulcer prevention (62 %). For risk reduction, we found esomeprazole being prescribed instead of pantoprazole; esomeprazole is indicated for children under a year old., Conclusion: This study reflects one given day: 36.5 % of off-label prescriptions and 3.2 % of unlicensed prescriptions in a paediatric setting. Few risk reductions for off-label number prescriptions have been found. This work confirmed the necessity of carrying out further studies in children.

Rationale, Aims and Objectives: High-alert medications (HAMs) are medications that are associated with a high risk of serious harm if used improperly. The objective of this study was to identify paediatric HAM used in our institution and to identify safety measures for their use., Methods: The list of HAM and the list of safety measures that were introduced in our department were based on (1) a literature search; (2) a survey of health care professionals in our department including doctors, head nurses, nurses and pharmacists; and (3) the drug steering committee., Results: We found four lists of HAM based on a literature search, including 27 classes of pharmaceutical agents, and 63 common drug names. The response rate of the survey was 20.7% (230 of 1113). Some of the HAMs included in our list were not identified by the literature search. These included neuroleptic drugs, anti-malarial agents, antiviral agents, anti-retroviral agents and intravenous acetaminophen. The drug steering committee selected 17 HAM and highlighted 53 safety measures involving seven broad aspects of pharmacological management., Conclusions: This project was part of the new safety strategies developed in a paediatric hospital. We set out to make a list of HAM relevant to paediatrics with additional safety measures to prevent medication errors associated and a 'joker' system. The various safety measures, such as double-checking of HAM prescriptions, should be reviewed during the year following their implementation. This list, which was developed in our hospital specifically for use in paediatrics, can be adapted for use in other paediatric departments., (© 2014 John Wiley & Sons, Ltd.)

In an effort to preserve traditional medicine knowledge and to uncover information about disease patterns and treatment in the Lao People's Democratic Republic (PDR), linguistic experts have scanned centuries-old medical palm leaf manuscripts for disease entries. A list of more than 7000 diseases has resulted, shedding valuable light onto the medical history and traditional medicine heritage of the people of Laos, as well as providing an index for faster research into specific diseases and their traditional treatments.

1-Hydroxybisphosphonate derivatives of ciprofloxacin, gatifloxacin and moxifloxacin have been synthesized using Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction. The 1,2,3-triazol linked hydroxybisphosphonate derivative of ciprofloxacin exhibited antibacterial activity comparable to the parent antibiotic and all fluoroquinolone-bisphosphonates displayed osteotropic properties in a bone model., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The present investigation describes the preparation and characterization of novel biodegradable nanoparticles based on complexation of poly-gamma-glutamic acid (gamma-PGA) with bivalent lead ion. The prepared nano-systems were stable in aqueous media at low pH, neutral and mild alkaline conditions. The particle size and the size of the complexes were identified by dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. It was found that the size of the complexes depended on the pH and concentrations of gamma-PGA and lead ions. Particle sizes measured by TEM revealed that at low concentrations, nanosized particles were formed, however, at high concentrations of gamma-PGA and lead ions, the formation of large aggregates with a broad size distribution was promoted. The size of individual particles was in the range of 40-100 nm measured by TEM. The results from the DLS measurements showed that the low and high pH values in mixtures with high concentrations of gamma-PGA and Pb2+ ions favored the growth of large complexes. The gamma-PGA nanoparticles, composed of a biodegradable biomaterial with high flocculating and heavy metal binding activity, may be useful for various water treatment applications.

The present investigation describes the synthesis and characterization of novel biodegradable nanoparticles based on chitosan. Poly(ethylene glycol) dicarboxylic acid was used for intramolecular cross-linking of the chitosan linear chains. The condensation reaction of carboxylic groups and pendant amino groups of chitosan was performed by using water-soluble carbodiimide. The prepared nanosystems were stable in aqueous media. The structure of the products was determined by nuclear magnetic resonance (NMR) spectroscopy, and the particle size was identified by dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. It was found that biodegradable cross-linked chitosan nanoparticles experienced considerable swelling because of the length and flexibility of the cross-linking agent. The aqueous solutions or dispersions of nanoparticles were stable and clear or mildly opalescent systems depending on the ratio of cross-linking and molecular weight of chitosan, findings consistent with values of transmittance above 75%. Particle size measured by TEM varied in the range of 4-24 nm. In the swollen state, the average size of the individual particles measured by DLS was in the range of 50-120 nm depending on the molecular weight of chitosan and the ratio of cross-linking.

The present investigation describes the synthesis and characterization of novel biodegradable nanoparticles based on chitosan for biomedical applications. Natural di- and tricarboxylic acids were used for intramolecular cross-linking of the chitosan linear chains. The condensation reaction of carboxylic groups and pendant amino groups of chitosan was performed by using water-soluble carbodiimide. This method allows the formation of polycations, polyanions, and polyampholyte nanoparticles. The prepared nanosystems were stable in aqueous media at low pH, neutral, and mild alkaline conditions. The structure of products was determined by NMR spectroscopy, and the particle size was identified by laser light scattering (DLS) and transmission electron microscopy (TEM) measurements. It was found that particle size depends on the pH, but at a given pH, it was independent of the ratio of cross-linking and the cross-linking agent. Particle size measured by TEM varied in the range 60-280 nm. In the swollen state, the average size of the particles measured by DLS was in the range 270-370 nm depending on the pH. The biodegradable cross-linked chitosan nanoparticles, as solutions or dispersions in aqueous media, might be useful for various biomedical applications.

Purpose: Fundoplication has been used successfully to treat gastroesophageal reflux (GER) in the pediatric population. Although successful in many patients, there is a significant risk of complications and failure, especially in high-risk patients such as those with certain types of associated anomalies, diffuse motility disorders, chronic pulmonary disease, neurological impairment, and young infants. However, the results are poorer with children with severe pathologic lesion associated to reflux: tracheoesophageal cleft, esophagocoloplasty, and esophageal atresia (EA) with severe dysmotricity. In neurologically impaired children with neuromuscular incoordination and GER, Bianchi has proposed total esophagogastric dissociation (TED). The authors report the use of esophagogastric or esocologastric dissociation to control reflux in children with severe GER in other situations, such as EA, burn esophageal lesions having led to coloplasty and severe esotracheal cleft., Methods: The authors reviewed the patients operated on for an esogastric or cologastric disconnection between 1997 and 2002. It is a single center retrospective study. The initial diagnosis, previous surgical procedure, postoperative course, and follow-up results were studied., Results: Between September 1999 and June 2003, 13 TEDs were performed in 6 boys and 7 girls. The mean age for TED procedure was 35 months (range 14 days to 218 months). Indication for TED was severe persistent reflux in, respectively, 9 cases of EA (7 with coloplasty and 2 with preservation of the native esophagus after atresia repair, associated in 1 case with an esotracheal cleft), 2 cases of esotracheal cleft type III, and 2 cases of esophagocoloplasty for caustic burns. Six patients had undergone previous fundoplications (1-4 procedures) that failed, whereas the remaining patients underwent TED as the primary antireflux procedure. The average follow-up was 26 months (range 1 month to 4 years). There were no complication during the immediate postoperative course. Three children died at 3, 4, and 12 months after the procedure from acute respiratory failure. Respiratory status was improved in 8 children, and recurrent bronchitis was noted in 1 child. Regarding the digestive status, gastrostomy was closed at 18 and 24 months in 2 children, and partial nocturnal enteral nutrition (200 to 900 mL/d) through the gastrostomy remains necessary in the other children., Conclusion: Total esophagogastric dissociation procedure improves the respiratory consequences of severe GER, particularly in children for whom other surgical treatments have failed. The long-term safety of this operation remains to be determined especially regarding the consequences of a gastrointestinal Roux-en-Y loop procedure.

Background: The risk of osteomyelitis after open bone fracture may be reduced by locally applied antibiotics. ENC-41-HP (E41), which comprises ciprofloxacin linked to a 'bone seeking' bisphosphonate, loaded on to carrier Skelite calcium phosphate granules (E41-Skelite) has favourable in vitro characteristics for application to wounded bone. This study assessed E41-Skelite in a rat model of acute tibial osteomyelitis., Methods: Mechanically induced tibial troughs were contaminated with approximately log10 4 colony forming units (c.f.u.) of Staphylococcus aureus (Cowan 1 strain) 'resistant' to E41 (minimum inhibitory concentration 8-16 microg/ml), lavaged and packed with Skelite alone, or with E41-Skelite slurry. Animals were killed at 24 h (n = 62), 72 h (n = 46) or 14 days (n = 12), and each tibia was assessed for S. aureus load (c.f.u./g tibia) and histological appearance (14 days only)., Results: At 24 and 72 h, the tibias of rats treated with E41-Skelite (n = 54) had a significantly lower mean (s.e.m.) load of S. aureus than animals that received Skelite alone (n = 54): log10 3.6(0.2) versus 6.4(0.1) c.f.u./g respectively at 24 h (P < 0.001, Mann-Whitney rank sum test) and log10 4.4(0.2) versus 6.6(0.1) c.f.u./g at 72 h (P < 0.001). At 14 days, E41-Skelite-treated tibias had fewer bacteria, no signs of osteomyelitis and histological signs of healing., Conclusion: E41-Skelite, a prototype granulated topical antibiotic delivery system, reduced the development of infection in experimental bone wounds., (Copyright 2004 British Journal of Surgery Society Ltd.)

Bisphosphonates conjugated to fluoroquinolone antibacterials through an intermediate carbon had better activity than conjugates lacking the carbon. Virtually all molar-based activity of these esterified bisphosphonate derivatives was identical to that of its parent. De-esterified free-acid forms retained good activity against most Gram-negative bacteria, but not against Gram-positives. A free-acid derivative remained bound to washed bone and completely inhibited Staphylococcus aureus growth. The more potent parent, ciprofloxacin, failed to bind significantly, and bacterial growth occurred.

Unlabelled: New issues have arisen in pediatric intensive care units, especially concerning long-stay patients. The aims of the present study were to describe the etiologic factors of these long-stay patients and to recognize the comorbidities., Material and Methods: Ninety-five patients who had a total of 100 hospitalizations of more than 30 days were admitted to the pediatric intensive care unit at Robert-Debre Hospital during a 3-year period (1993-1995); this accounted for 9.1% of total admissions. We retrospectively reviewed these 100 long-stay hospitalizations., Results: Most of these patients were newborns (65%). Patients with severe congenital anomalies (44 patients) and very premature infants (26 patients) constituted the majority of long-stay patients. The mean duration of mechanical ventilation for the 95 patients was 110 days (ranges 17-789 days). Two factors of comorbidity were found: gastroesophageal reflux (41% of cases) and nosocomial infections (89% of cases)., Conclusion: In order to prevent long stays, pediatric intensive care units must be directed toward these factors.

Acylation of amoxycillin and cephalexin with acids III, V and VII, and with isocyanate VIII furnished the corresponding beta-lactam antibiotics (X and XIII-XV, respectively). The antibacterial activity of these new antibiotic analogues against Helicobacter pylori was found to be identical with those of amoxycillin, Augmentin, erythromycin and ciprofloxacin.

The prognosis of antenatally diagnosed congenital diaphragmatic hernias (CDH) is clearly related to the degree of pulmonary hypoplasia (PH). After birth, controversies remain regarding the implementation of various therapies, especially the use of extracorporeal membrane oxygenation (ECMO). In the literature, the persistence of a Pao2 below 100 mm Hg and of Paco2 above 40 mm Hg despite optimal conventional therapy indicates poor prognosis. Therefore, since 1992, published and personal experiences led the authors to exclude CDH patients from ECMO when conventional therapy (including high-frequency oscillatory ventilation and nitric oxide) did not obtain Pao2 of above 80 mm Hg and Paco2 of below 60 mm Hg. The aim of this retrospective study is to determine whether blood gas results correlate with postmortem findings. Between July 1990 and July 1994, 32 cases of CDH were monitored antenatally and managed postnatally at the authors' institution. Six patients survived; 26 died, including one immediately at birth. Thirteen were treated by ECMO. Seventeen had a best Pao2 of above 80 mm Hg, including the six survivors. Fourteen did not reach this level, and none of them survived. Twenty-three infants underwent postmortem examination. PH was assessed using two criteria: (1) lung weight to body weight ratio (LW/BW) and (2) radial alveolar count (RAC). Two patients did not have hypoplasia (LW/BW > 0.018). Twenty-one patients had PH; 12 of them had an LW/BW ratio of less than .009; for 9, the LW/BW ratio was between .009 and .018, and the RAC (< 3.1) confirmed PH. All infants with a best Pao2 of less than 80 mm Hg had PH. Patients with a best Pao2 of greater than 80 mm Hg included two infants who died from complications without PH, eight infants with demonstrated PH, and the six survivors. In conclusion. (1) No infant with nonhypoplastic lungs has been deprived of ECMO by the authors' criteria. (2) Adequate values of blood gases may not eliminate PH. Therefore, this probably justifies starting ECMO when conventional therapy fails. (3) Conversely, permanent poor values of Pao2 allowed the prediction of PH in all cases. Such patients probably can be excluded from ECMO treatment.

The authors report a rare case of cannula thrombosis during extracorporeal membrane oxygenation (ECMO). A full-term newborn infant was successively placed on single-cannula veno-venous extracorporeal lung support and then on veno-arterial ECMO, because of persistent pulmonary hypertension. At 140 hours of ECMO, the infant displayed general cyanosis except in the right arm. Since asymmetric hypoxemia during ECMO may be related either to cannula malposition or to a tip thrombosis, a chest x-ray after contrast injection into the arterial line of the circuit was performed. It showed an opacification of the whole cannula but for the last distal centimeter, and of the vascular bed extending from the right subclavian artery. Cannula thrombosis was suspected and confirmed by removal of the arterial cannula. Demonstration of cannula thrombosis by opacification of the arterial line of the circuit indicates catheter removal.

Because disordered autoregulation of cerebral blood flow may underlie neurologic injury associated with cardiopulmonary bypass (CPB), we studied the effects of normothermic (37 degrees C) and hypothermic (18 degrees C) CPB on cerebral vascular reactivity in 6 to 8-week-old piglets. Hypothermic CPB animals were subdivided into alpha-stat and pH-stat groups (n = 6 animals each group) according to acid-base management protocol. Cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), cerebral vascular resistance (CVR), and CBF response to hypercapnia were examined before, during, and 1 hour after CPB and used to calculate CVR per millimeter of mercury change in arterial partial pressure of CO2: (CVRnormocapnia - CVRhypercapnia)/(PaCO2 hypercapnia - PaCO2 normocapnia). Before CPB, CBF, CMRO2, and vascular reactivity to elevated CO2 were similar in the three groups; these parameters remained unchanged by normothermic CPB. However, during hypothermic CPB, CBF and CMRO2 decreased in both alpha-stat and pH-stat groups; in the alpha-stat group, CBF decreased from 27 +/- 5 mL.min-1.100 g-1 (normothermic CPB) to 5 +/- 1 mL.min-1.100 g-1 (hypothermic CPB) (p < 0.05) and CMRO2 decreased from 1.8 +/- 0.21 to 0.24 +/- 0.04 mL.min-1.100 g-1 (p < 0.05), whereas in the pH-stat group CBF decreased from 28 +/- 2 to 9 +/- 1 mL.min-1. 100 g-1 (p < 0.05) and CMRO2 decreased from 1.63 +/- 0.07 to 0.31 +/- 0.09 mL.min-1.100 g-1 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Despite advances in ventilator management and use of extracorporeal lung support, mortality related to ARDS in pediatric patients has not been reduced over the past 20 years. Progressive respiratory failure, due to evolution of the primary illness or to complications of ventilator therapy, significantly contributes to poor outcome. ARDS is characterized by severe ventilation-perfusion mismatch and by pulmonary hypertension. Because of their side effects which affect systemic hemodynamic status or worsen intrapulmonary shunting, intravenous vasodilator trials have been of limited interest. Nitric oxide (NO) has been recognized as a gas with vasodilator properties. In neonates studies have shown that inhaled NO may have an important role in the therapy of persistent pulmonary hypertension. Inhaled NO in adults with severe ARDS has been shown to reduce pulmonary hypertension without producing systemic vasodilation. This reduction of pulmonary vascular resistances may reduce pulmonary edema formation, decrease vasoconstrictor response to cardiotonic agents, and improve biventricular function. In addition, arterial oxygenation seems to be increased by improved matching of ventilation with perfusion. Improvement of oxygenation with inhaled NO suggests that use of lower tidal volumes and FIO2 may be more successful. Until now, there are no published studies regarding NO administration in ARDS affecting nonneonatal pediatric patients. However, the results obtained in adults and newborns suggest that inhaled NO may be a useful adjuvant therapy of ARDS in children, possibly in association with other therapies. Even in adults it remains unclear whether therapy with inhaled NO can reduce morbidity and mortality. Prospectives and randomized studies are essential to assess the real utility of inhaled NO in ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal lung support (ECLS) for newborns with acute respiratory failure has achieved increased popularity over the last decade. However, precise criteria for its implementation remain controversial. The aim of this study was to assess the value of Doppler echocardiography (DE) in 31 neonates with PaO2 of < or = 50 mmHg, FIO2 of 1, and optimal ventilation. Treatment included mechanical ventilation, paralysis, volume loading, vasopressors, and tolazoline. Markers indicative of ECLS (failure of maximal medical therapy, assessed by AaDO2 of more than 610 mm Hg beyond 8 hours and/or an oxygenation index (OI = mean airway pressure x FIO2%/postductal PaO2) of more than 40 beyond 4 to 6 hours) were present in 23 (group 1) and absent in eight (group 2). Shunt direction and systolic pulmonary arterial pressure (sPAP) calculated from tricuspid insufficiency velocity were assessed using DE. At the time of admission, sPAP was significantly higher in group 1 (62.1 v 43.7 mm Hg). On day 1, group 1 differed from group 2 in maximum sPAP value (73.2 v 44.4 mm Hg), PaCO2 (56.1 v 40 mm Hg), right-to-left shunting (85% v 25% of the patients), and pulmonary-to-systemic-pressure systolic ratio (sPAP:sSAP) (1.29 v 0.75). Patients with an sPAP:sSAP ratio of more than 1 and patients with high sPAP associated with high PaCO2 on day 1, all later (average, 10 hours later) fulfilled ECLS criteria; this suggests that DE assessment of pulmonary circulation may yield early and predictive markers of impending ECLS indication. Further confirmation of these results would help avoid unnecessary delays in ECLS implementation in newborns with severe respiratory failure.

Background: There have been several reports that prolonged exposure of pregnant women to indomethacin for tocolysis may have significant pharmacological effects on the fetus or newborn., Patients: Eighteen pregnant women were given indomethacin during the year 1989 for treatment of premature labor (n = 16) or polyhydramnios (n = 2). Treatment was started at gestational week 28.1 +/- 2.5 and was discontinued at gestational week 30.7 +/- 1.8. The mean age of the women at the onset of pregnancy was 30.6 +/- 5.3 years. The daily dose of indomethacin was initially 200 mg (2-3 mg/kg), then 107 +/- 59 mg. The cumulative dose was 1,820 +/- 2,370 mg. The duration of treatment was 18.1 +/- 16.4 days (less than 7 days in 8 women)., Results: The term at delivery was 33.4 +/- 3.3 weeks (11 after 32 weeks). The mean interval between discontinuation of treatment and delivery was 19.0 +/- 18.7 days. Indomethacin was effective in 10 cases of premature labor, and gestation was prolonged by 52.6 +/- 19.2 days. Among the 23 live-born neonates, 5 developed renal insufficiency attributed to indomethacin (4 premature labor, 1 hydramnios). The kidney failure with early hyperkalemia was cured within about 7 days in 4 cases. The remaining neonate also suffered from severe prolonged hypoxia and died on day 4., Conclusions: Administration of indomethacin for premature labor places the fetus at risk because of the short drug-free interval before birth. High daily or cumulative doses of indomethacin dit not result in adverse effects.

The tunicas media and adventitia can be isolated, intact, from the rat carotid artery by simple mechanical extrusion. While morphologically normal, when incubated for 24 hr in vitro in appropriate radioactive precursor the isolated layers synthesized DNA, RNA and protein at very low levels which was only a fraction (5-15%) of that synthesized by the intact vessel.

Background: Neonates with classic maple syrup urine disease (MSUD) undergo rapid neurological deterioration by the end of the first week of life. Exchange transfusion and peritoneal dialysis are the usual emergency treatment. Continuous arteriovenous hemofiltration (CAVHF) appears to be safe and more rapidly effective., Case Report: Martin was born at the 37th week from a normal pregnancy. Abnormal movements of legs and lethargy appeared on the 7th day of life. Progressive brain dysfunction with coma led to intubation on the 13th day. A diagnosis of MSUD was immediately made and CAVHF was initiated and continued for 19 hours. The plasma leucine, valine and isoleucine levels fell from 2,248 to 275, 640 to 91 and 298 to 13 mumol/l, respectively. Neurologic improvement was dramatic, except for moderate hypertonia which lasted for the 2 following days., Conclusion: CAVHF is an appropriate treatment for very young patients with inborn errors of metabolism. It appears safer and more rapidly effective for eliminating branched-chain amino acids than other techniques, such as peritoneal dialysis with or without exchange transfusions. It also permits more rapid introduction of the specific diet.

The influence of growth and aging on the synthesis of DNA, RNA and protein in the myointima in vivo was explored by incubating isolated myointima of different ages in labelled precursors. As myointima grew and aged in vivo, the rates of DNA and protein synthesis declined, while the quantity of DNA increased more than two-fold in seven days. The rate of RNA synthesis remained constant and was unaffected by growth. Like that of DNA and protein synthesis, fetal bovine serum was not required by the isolated myointima to synthesize RNA in vitro. Taken together, these findings confirm and extend our previous results which showed the synthetic autonomy of the isolated myointima, and demonstrate further that during growth the synthesis of RNA is affected in a manner that differs from that which controls DNA and protein.

Seventy-two patients with congenital diaphragmatic hernia (CDH) diagnosed in the first 12 hours of live have been reviewed retrospectively. Forty-eight patients born before 1985 (group I) were compared to 24 patients born between 1985 and 1989 (group II). The management was different for the 2 groups. Group I was operated on immediately. For group II, delayed surgery after stabilization was preferred. For this group, stability was sought before, during and after surgery. Therapy was first aimed at optimizing ventilation and oxygenation by way mechanical ventilation. Pharmacologic agents were used in an attempt to decrease pulmonary vascular resistance and improve cardiac output. The survival rate was 37.5% before 1985, 62.5% after 1985 (P less than 0.01). Main prognostic factors were Apgar score, paCO2, pH, ventilation index, alveolar-arterial difference in oxygen and oxygenation index. The stabilization before surgery improved the survival rate.

The myointima, which forms within the lumen of the carotid artery of the rat in response to the removal of the endothelium by a balloon catheter, could be extruded from the vessel as early as 6 days after denudation. The mean concentration of DNA in the isolated myointima increased as the myointima grew in vivo until 12 to 14 days after denudation, when the arterial lumen was filled with the myointima; thereafter the mean concentration of DNA declined. DNA and protein synthesis, incorporation of 3H-glucosamine and 3H-fucose into macromolecules, occurred in the myointima during incubation in vitro in the absence of fetal bovine serum, and with the exception of 3H-glucosamine, failed to be stimulated by it. These data indicate that the cells of the intact myointima do not require exogenous macromolecular growth factors for the synthesis of macromolecules in vitro.

Insulin therapy, administered by continuous subcutaneous infusion with osmotic pumps over a 28 day period at doses of 2.5 and 5.0 units/day, resulted in a statistically significant increase in body weight of diabetic rats. The concentration of blood glucose was reduced by 68% to 109 mg/dl blood sugar by the higher dose of insulin and only partial control of diabetes was achieved by the lower dose (185 mg/dl blood sugar, -39%). Blood pressure was normalized by both doses of insulin. Elevated serum angiotensin converting enzyme activity and plasma renin activity, expressed as generated angiotensin I, were unaffected by the lower dose of insulin, but were reduced by 26% and 40%, respectively at the higher dose. These data suggest that elevated serum ACE and plasma renin activity, commonly found in the streptozotocin-diabetic rat, may not be primarily responsible for hypertension in this model.

Reliable in vitro tests are needed to study the epidemiology, pharmacology, genetics and the treatment of Falciparum malaria. We have studied the reproducible nature of an in vitro method using either patients blood or a continuous strain with which we did 254 chemosensitivity tests with chloroquine, mefloquine and quinine. The method is based on ED50 determination which is done by assessing the plasmodial maturation on thin blood film after 24-48 hours incubation. This method is simple to carryout but long to interpret. It has proved reliable and sensitive enough to be used for the proposed studies. The blood group, the limited variations of erythrocyte concentrations, of the composition and volume of the culture medium, of the atmosphere and of the incubation time had little influence on the ED50. It was considered that 47 p. cent of the tests could be interpreted and that this percentage could be improved with a better understanding of the in vitro behaviour of P. falciparum.

A one-month old infant whose mother had been treated with erythromycin during pregnancy exhibited signs of severe congenital syphilis with collapse requiring admission to an intensive care unit. Erythromycin has low placental transfer and other treatments would have probably been more adequate. Some authors advocate the use of the latest tetracyclines and doxycycline could also be administered. The WHO's recommendations that all children born of mothers who were not treated with penicillin should receive this antibiotic after birth is still valid.

The penetration of the zona-pellucida by hamster sperm in vitro (assay drops) was inhibited by aliquots of ultrafiltrates obtained from another set of drops (experimental drops) in which capacitated sperm had interacted with the surface of the zona pellucida. This inhibition was inversely related to the concentration of sperm in the assay drop, and it was noted that the inhibitory response declined when the gametes in the assay drop were incubated together beyond the standard 90-min period. Thus, inhibition was not irreversible. A number of criteria suggest that the inhibitory activity resides in at least some of the peptides (S1 factors) released at four different times after contact between the surfaces of the sperm and zona pellucida. Like the S1 factors, the substances responsible for the inhibitory activity of the supernatants, collected at 2 and 50 min after gamete combination, traversed ultrafilters with Mr cutoffs of 5000 and 2000, respectively, and were inactivated by subtilisin. In addition, the quantity of inhibitory material recovered in the ultrafiltrates from experimental drops containing various numbers of eggs was well correlated with the amount of 2- and 50-min S1 factors from similar experimental drops. These results suggest that the S1 factors are peptide modulators of the penetration process and it is speculated that one of their functions may be to prevent or at least to discourage polyspermic penetration of the hamster zona pellucida.

Normal gerbils and those made ischemic for 15 to 60 minutes by bilateral common carotid artery occlusion were studied ultrastructurally after administration of the vasoactive drug pentoxifylline. In both groups, hypertrophy of neuronal mitochondria was found in the hippocampus and cerebral cortex. Planimetry of electron micrographs revealed a statistically significant increase in average mitochondrial size of drug-treated animals compared with untreated ischemic gerbils and normal controls; the treated ischemic group showed the greatest increase. Incubated cortical slices from normal gerbils that were given the drug 5 hours before they were killed showed a significant increase in oxygen consumption compared with controls.

Meningococcal shock still is associated with high mortality. Along with antibiotics and control of metabolic derangements, standard therapy involves monitoring and maintaining numerous cardiorespiratory variables. From 1980 to 1985, 39 children with meningococcal shock were treated in our pediatric ICU. We obtained full hemodynamic monitoring in 18 (12 survivors, six nonsurvivors). Two hemodynamic patterns were observed: hypovolemia and cardiac failure. Early death was generally related to refractory hypovolemia, probably secondary to severe capillary leak. Survival usually occurred when noticeable cardiac failure was controlled with early use of catecholamines and judicious fluid management. Because cardiac failure only slowly recovered, a therapeutic approach that aims not at normal variables but, rather, at survival variables seems appropriate.

A case of intestinal obstruction and enterocolitis, probably as a consequence of inappropriate use of thickened feedings, is reported. Products which thicken feedings take an important part in the treatment of gastro-oesophageal reflux in infants. In order to thicken feedings, pectin and silicium have been added to milk. However, they may lead to an obstructive medication bezoar. Thus, it is necessary to limit their use to 3-5% of feeding and to clearly explain their potential hazards to the family.

Lead encephalopathy was induced in suckling rats by administering lead to the mother. The brains were studied by light and electron microscopy, and the results were compared with observations in the human disease as well as in cases of cerebral ischemia in children. In their severe forms, both human and experimental lead encephalopathies are characterized by exudative extracellular edema and perivascular PAS-positive globules. The latter consist of osmiophilic non-membrane-limited cytoplasmic inclusions located, in the rat exclusively and in the human predominantly, in perivascular astrocytes. Intervascular strands are also found in both forms of the disease. In the rat these consist of basement membrane surrounding endothelial cytoplasm. Chemically, experimental lead encephalopathy with morphologically demonstrable edema is associated with an increase in brain water, sodium and serum albumin. Relative to the serum concentration, the increase in water is disproportionately greater than the sodium or albumin. There were no demonstrable changes in chloride or potassium.

The activity of four antimalarial drugs against 66 Plasmodium falciparum isolates from 15 countries was assessed by an in vitro semi-microtest. Median inhibitory concentrations (IC50) for chloroquine were less than 120 nM in 22 isolates from patients successfully treated with chloroquine, and more than 250 nM in six isolates from patients with chloroquine-resistant malaria. 10 of 15 isolates from Brazil (Amazonia), 7 of 12 isolates from Madagascar, two from Kenya and two from Thailand had IC50 for chloroquine of more than 250 nM. None of the 35 isolates from West and Central Africa had IC50 of more than 120 nM. Very different levels of sensitivity were observed in Brazil and Madagascar. 27 of 28 isolates (including two that were chloroquine-resistant in vivo) had IC50 of less than 50 nM for dichlorquinazine, a 4-aminoquinoline. The IC50 for mefloquine was less than 160 nM in 55 isolates including ten from patients who were successfully treated with mefloquine. IC50 for quinine were between 140 and 660 nM for 30 isolates. This test has proved useful in epidemiological studies, therapeutic monitoring of clinical cases and in the evaluation of new drugs.

A convenient organ culture system is described in which fragments of mucous membrane isolated from bronchi of the pig were maintained in either screw-cap tubes or multiwell tissue culture plates. The mucous membrane of the pig bronchus, like that of the human, is rich in mucus-secreting submucosal glands and can respond to cholinergic stimulation in vitro by releasing either L-[3H]fucose- or L-[3H]serine-labeled acid-precipitable macromolecules. Reproducible cholinergic-mediated release of labeled macromolecules was attained by first washing the mucous membrane fragments in serum-free modified Earles medium (Dulbecco's) for 120 min at 4 degrees C. Maximum stimulation was obtained when the incubation medium was supplemented with 0.5-2.0% horse serum. Approximately 50% of L-[3H]fucose-labeled macromolecules were eluted in the void volume from a column of Sepharose CL-6B in 6 M urea. Cochromatography of L-[3H]- and L-[14C]fucose-labeled glycoproteins released by mucous membranes of control and methacholine-treated tissue fragments failed to reveal any significant difference in any specific population of fucose-labeled glycoproteins. It is concluded that, as a whole, many different labeled molecules are released in response to cholinergic stimulation. Taken together, these results suggest that the mucous membrane of the porcine bronchus is a useful in vitro model for studying respiratory mucus secretion.

An "in vivo" method for non-invasive determination of cerebral venous hemoglobin O2 saturation (SvO2) was developed. A specially designed spectrophotometer recorded the Td near IR spectra of transilluminated brain tissue surrounding the SS. The accuracy of the method, based on the principle of DNIRS was tested on eight pentobarbital anesthetized dogs during hypoxic hypoxia (inspired O2 6-21%). Spectral data were transformed into first derivative for correlation with SvO2 data measured from the SS. Linear regression analyses were applied using data from 5 dogs, with SvO2 ranging from 1.5%-70%, to build a 3 wavelength algorithm for predicting brain SvO2. In three dogs, this regression equation was employed to predict SvO2 in 31 separate spectra of varying HH intensity. The standard deviation of differences between SvO2 and predicted values was 3.2%. The predicted values, when regressed against the sampled SvO2, yielded an r value of 0.97. The results demonstrate that it is possible to noninvasively quantify SvO2 utilizing IR spectroscopy.

Lead subacetate (0.5g) and 1000 units of vitamin D were given three times a week to four newly-weaned rhesus monkeys. In addition, two animals received only the vitamin D. The poisoned animals had an increase in the urinary excretion of delta-aminolevulinic acid, an elevated content of lead in the blood, and a fall in hemoglobin concentration. Between 6 and 18 weeks the animals suddenly developed ataxia, nystagmus, generalized weakness, and convulsions. At this time the animals were killed by perfusion of fixative and the brain prepared for light and electron microscopic studies. Definite morphological evidence of disease was confined to the central nervous system, except for one animal which showed the characteristic renal inclusions of lead poisoning. All animals showed PAS-positive globules associated with blood vessels and an exudative edema involving the white matter of the cerebral hemispheres and cerebellum. Ultra-structurally, this appeared as a granular precipitate within an expanded extracellular space. Alterations of nerve fibers were not seen in the white matter but axonal swelling was observed in the cerebral cortex. The perikaryon and neuropil appeared normal. The control animals showed no significant cerebral changes.